3WBL
Crystal structure of CDK2 in complex with pyrazolopyrimidine inhibitor
Summary for 3WBL
| Entry DOI | 10.2210/pdb3wbl/pdb |
| Related | 3A2C |
| Descriptor | Cyclin-dependent kinase 2, ACETATE ION, N~7~-(4-ethoxyphenyl)-6-methyl-N~5~-[(3S)-piperidin-3-yl]pyrazolo[1,5-a]pyrimidine-5,7-diamine, ... (4 entities in total) |
| Functional Keywords | binding sites, tumor, cyclin-dependent kinase 2, drug design, map kinase kinase 2, mk2, protein kinase inhibitors, pyrazoles, pyrimidines, structure-activity relationship, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm, cytoskeleton, microtubule organizing center, centrosome: P24941 |
| Total number of polymer chains | 1 |
| Total formula weight | 34401.99 |
| Authors | Fujino, A.,Fukushima, K.,Kubota, T.,Kosugi, T.,Takimoto-Kamimura, M. (deposition date: 2013-05-20, release date: 2013-10-30, Last modification date: 2023-11-08) |
| Primary citation | Fujino, A.,Fukushima, K.,Kubota, T.,Kosugi, T.,Takimoto-Kamimura, M. Crystal structure of human cyclin-dependent kinase-2 complex with MK2 inhibitor TEI-I01800: insight into the selectivity. J.SYNCHROTRON RADIAT., 20:905-909, 2013 Cited by PubMed Abstract: Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2) is a Ser/Thr kinase from the p38 mitogen-activated protein kinase signalling pathway and plays an important role in inflammatory diseases. The crystal structure of the MK2-TEI-I01800 complex has been reported; its Gly-rich loop was found to form an α-helix, not a β-sheet as has been observed for other Ser/Thr kinases. TEI-I01800 is 177-fold selective against MK2 compared with CDK2; in order to understand the inhibitory mechanism of TEI-I01800, the cyclin-dependent kinase 2 (CDK2) complex structure with TEI-I01800 was determined at 2.0 Å resolution. Interestingly, the Gly-rich loop of CDK2 formed a β-sheet that was different from that of MK2. In MK2, TEI-I01800 changed the secondary structure of the Gly-rich loop from a β-sheet to an α-helix by collision between Leu70 and a p-ethoxyphenyl group at the 7-position and bound to MK2. However, for CDK2, TEI-I01800 bound to CDK2 without this structural change and lost the interaction with the substituent at the 7-position. In summary, the results of this study suggest that the reason for the selectivity of TEI-I01800 is the favourable conformation of TEI-I01800 itself, making it suitable for binding to the α-form MK2. PubMed: 24121337DOI: 10.1107/S0909049513020736 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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